Tumor Selective Metabolic Reprogramming as a Prospective PD-L1 Depression Strategy to Reactivate Immunotherapy
- 주제(키워드) immunotherapy , mitochondria , photodynamic therapy , programmed death ligand-1 , tumor targeting
- 주제(기타) Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter
- 설명문(일반) [Liu, Yu; Zhou, Zaigang; Hou, Jiting; Chen, Jiashe; Zheng, Chunjuan; Shen, Jianliang] Wenzhou Med Univ, State Key Lab Ophthalmol Optometry & Vis Sci, Sch Ophthalmol & Optometry, Sch Biomed Engn, Wenzhou 325027, Peoples R China; [Zhou, Zaigang; Hou, Jiting; Shen, Jianliang] Univ Chinese Acad Sci, Wenzhou Inst, Wenzhou 325000, Peoples R China; [Xiong, Wei] Cent South Univ, Dept Urol, Xiangya Hosp 3, Changsha 410013, Peoples R China; [Kim, Heejeong; Yoon, Juyoung] Ewha Womans Univ, Dept Chem & Nanosci, Seoul 03760, South Korea; [Jiang, Xin] Cent South Univ, Dept Urol, Xiangya Hosp, Changsha 410008, Peoples R China
- 등재 SCIE, SCOPUS
- 발행기관 WILEY-V C H VERLAG GMBH
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000202993
- 본문언어 영어
- Published As https://doi.org/10.1002/adma.202206121
- PubMed https://pubmed.ncbi.nlm.nih.gov/36017886
초록/요약
Currently, the role of the lysosome, endoplasmic reticulum, or dictyosome in the transcription and translation of programmed cell death ligand 1 (PD-L1) is well revealed, but the role and function of mitochondria in the PD-L1 expression in tumors is still not fully researched, making it hard to offer a novel PD-L1 regulation strategy. In this research, it is newly revealed that mitochondria oxidative phosphorylation (OXPHOS) depression can be used as an effective PD-L1 down-regulation method. To offer an ideal and high-effective tumor mitochondria-targeted OXPHOS depression nanosystem, IR-LND is prepared by conjugating mitochondria-targeted heptamethine cyanine dye IR-68 with mitochondrial complexes I and II depression agent lonidamine (LND), which then further self-assembled with albumin (Alb) to form IR-LND@Alb nanoparticles. By doing this, PD-L1 expression in tumors is selectively and effectively depressed by IR-LND@Alb nanoparticles. As expected, the anti-tumor efficacy of such a PD-L1 depression strategy is superior to conventional anti-PD-L1 monoclonal antibodies. Interestingly, IR-LND can also be served as a novel ideal promising photodynamic therapy (PDT) drug with self-oxygen and self-PD-L1 regulation capacity. All in all, this tumor-selective metabolic reprogramming platform to reactivate immunotherapy and sensitize for PDT effect, would open a new window for mitochondrial immunotherapy for cancer patients.
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